An inframe mutational analysis of the v-rasH oncogene of Harvey murine sarcoma virus has indicated that most hydrophilic regions of the protein it encodes are dispensable for transformation by NIH 3T3 cells. One of these regions, which probably represents an area of the protein that interacts directly with its cellular target (S), is required for biological activity. In Harvey murine sarcoma virus, an enhancer region located outside the viral LTR has been identified. This enhancer element plays a major role in determining the pathology induced by the virus. In the studies of the Bovine papillomavirus genome, the second transforming gene of this virus has been identified as being encoded by the E5 open reading frame. The E1 open reading frame has been shown to inhibit the induction of cell transformation by BPV. A polypeptide encoded by the E2 open reading frame has been found to bind directly to multiple sites located within the upstream regulatory regions of the BPV and HPV16 genomes, suggesting that the enhancer activity of the E2 gene product on the viral genome is mediated via this direct interaction with viral DNA.